This proposal, a collaborative effort involving investigators in basic and clinical departments at Harvard Medical School (HMS) and several of its major teaching affiliates, seeks support to establish a multidisciplinary institutional Physician-Scientist Program with special emphasis on organ systems and diseases which are central to the mission of the National Institute of Arthritis, Metabolism, Digestive and Kidney Diseases (NIADDK). The principal goal is to provide young physicians with an opportunity to engage in an in-depth (5 year) course of didactic academic training and intensive laboratory experience in basic and clinical sciences. Typical postdoctoral trainees will have completed two years of housestaff training and will be selected on the basis of demonstrated excellence in prior endeavors, performance during interviews with members of The Program Committee and a strong commitment to a career in academic medicine and research. This program also seeks to provide highly qualified and motivated third and fourth year medical students with a similarly intensive but less prolonged (one or two years) didactic and investigative experience so as to encourage their interest in a future career in academic medicine and biomedical research. We view this new program as complementing, rather than competing with, those already available locally [(i.e., NIH-supported Medical Scientist Training Program at HMS; Harvard-MIT Division of Health Sciencies and Technology; Postdoctoral Fellowship Training Programs (primarily through individual or institutional National Research Service Awards in various clinical departments)]. By formalizing the quality and scope of this experience so as to ensure rigorous didactic study and laboratory training in basic and clinical research, it is expected that the Physician-Scientist Program as implemented at this institution will foster the development of a pool of full time academic physician-investigators capable of applying state-of-the-art techniques and concepts of basic science to the elucidation of disease mechanisms in areas supported by NIADDK and to be able to compete successfully for such support.